by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
It Started With An Email
About a year ago an email came across my desktop. “Hey man, I got gyno again.” My friend had gynecomastia from using steroids previously, but this time he was only taking prohormones. The product was supposed to contain only 19-nor-androstenedione. Since, then about 40 or so complaints of gyno from a variety of prohormones have surfaced across my desktop. After talking with various manufacturers, reviewing the scientific literature, and reading through some studies, here are some potential reasons why men may be getting gyno from these supplements.
Filled With Junk
Several supplement manufacturers have reported that the purity of prohormone products is pretty sad. Estimates have surfaced that androstenediol products generally contain less than 80% of the label claim, so a 250 mg. capsule may contain 200 mg. or less of the prohormone. Various studies have reported similar results, but the methods of analysis were not always reported. Without knowing how the supplements were analyzed, the information is more akin to a rumor. Since published studies have indicated that a variety of products (like ginseng and gingko biloba) don’t have any active ingredients in them [1], and that Ephedra [2, 3] and yohimbe [4] products contain inconsistent alkaloid contents, we can expect similar problems with prohormones. The supplement industry has a terrible reputation for offering hyped-up marketing promises while producing junky products. Getting back to the rumors of junky prohormones, one has to wonder what makes up the rest of the product? The rest of the product may contain anything from filler material to an array of different prohormone compounds. The problem here is that without knowing what is in the product, consumers can not control what they are taking. The other concern is that if a company is so sloppy to offer a product that does not meet label claims, maybe the product also has contaminants in it. In order to know if your product has impurities in it, you need to see the lab results from tests for impurities. At this point in time you shouldn’t buy products by name or price, but buy products that offer proof of the label claim and that are tested for contaminants. Ideally, independent labs would test these products and publish the results so everyone would know which products to avoid. Fear of retaliation by lawsuits prevents this from happening. Some supplement retailers were getting products tested and posting the results, but they still sold the junky products. It would make more sense if the supplement retailers who tested the products screened out the junk before it gets to their shelves or in the consumers’ hands, not just sell it anyway. They should also publish the information so that people will find out what to avoid taking.
Stacks
The mentality of stacking different steroids to achieve a desired effect has firmly implanted itself in the minds of supplement takers. While some supplements may work synergistically, we can also be quite certain that other supplements may work antagonistically. Lots of prohormone products contain up to six different prohormones in them. There is absolutely no research on how these agents will interact in people. The rationale used many times is that the different hormones will use different enzymes and one can experience a synergistic effect by creating testosterone or nortestosterone simultaneously. However, we can’t put something into our bodies and tell it what to do or where to go. The body transports prohormones to different tissues where they may compete for the same enzymes in order to be converted into a more anabolic compound. By ingesting too many different prohormones, or too much of the same prohormone, users may saturate one pathway and, in effect, be forcing prohormones down another pathway, like into the arms of aromatase. Aromatase is the enzyme that converts some androgens into estrogens. If prohormones are taken long enough and with high enough dosages, there certainly is the potential to cause gynecomastia. What most companies tell people is, “Take this product for X number of weeks and then discontinue for at least four weeks.” This is probably a prudent decision, but the problem is that, once again, there is no research to support or refute this approach.
The Wrong Mix
Take a look at your supplement label. Read how many different prohormones it has. Does it also have saw palmetto or some other herb that inhibits the 5-alpha-reductase enzyme (which converts testosterone into dihydrotestosterone and nortestosterone into dihydronortestosterone)? If so, throw it out. It is junk made by some company that hasn’t read the scientific literature. Many foolish supplement companies have played upon the fears of consumers by adding saw palmetto into their prohormone mix to minimize the potential for complications with the prostate gland. There are several factors that contribute to benign prostatic hypertrophy (BPH) and prostate cancer. DHT is just one of these factors. By preventing the body from balancing out androgen levels (ie converting some testosterone to DHT), more androgen (ie testosterone) will be converted into an estrogen (ie estradiol). This could have a potential role in the development of gynecomastia. So avoid prohormones with saw palmetto or other reductase inhibitors. There has also been a case report of finasteride (a reductase inhibitor) causing gyno [5].
Aside from ridiculous stacks making up the wrong mix, there are also ridiculous prohormones. 5-androstenediol (5AD) is one prohormone that makes little sense to take. It has been touted by supplement companies as a precursor to testosterone and capable of building muscle and improving strength. Research using isolated human prostate cells indicates that 5AD can bind to the androgen receptor directly and after conversion to testosterone [6]. This may sound like a good thing, but wait, there’s more. 5AD stimulates uterine growth in rats and breast cancer cells to proliferate, both classic estrogen-like effects [7, 8]. It has also been correlated with increases in breast cancer [9, 10]. To sum it up, there’s no real evidence that 5AD as a prohormone can increase muscular gains, but there is the real world potential of it acting as an estrogen. If you want to increase bodyfat and develop 36DD’s, 5AD may be for you.
Without beating a dead horse, two other potential estrogen enhancers are DHEA and androstenedione. DHEA binds to the estrogen receptor weakly, based on cell studies, and is not considered an estrogen agonist [11]. It elevates estrogen and testosterone levels in post-menopausal women [12] and elderly men [13]. The increase in estrogen appears to have a physiological effect, as the short term use of DHEA can correct impairments in bone turnover and menstrual function in young women with eating disorders [14]. Long-term studies seem to agree that DHEA may have benefit for the elderly, but differ on whether or not it can raise testosterone levels in men [13, 15].
DHEA can be converted into androstenedione (as well as 5AD). Androstenedione can easily be converted into estrone and then estradiol. A cell culture system using pig cells demonstrates that androstenedione can be converted into an estrogen [16] and a recent study in the Journal of the American Medical Association verifies that this happens in men as well [17]. The funny thing about the JAMA paper is that lots of criticism was raised against it, yet the people critiquing it didn’t stop to think about a few things. The first is that if you pick up any decent endocrine physiology book it will tell you that a good portion of androstenedione gets converted into estrone and then into estradiol in men. Next consider that these guys received Andro-6. The amount of Andro-6 (given in this study) was confirmed by an independent lab to contain 300 mg of androstenedione, 150 mg DHEA, 750 mg Tribulus terrestris, 375 mg chrysin, 300 mg Indole-3-carbinol (I3C), and 540 mg Saw palmetto. Now chrysin is supposed to block the conversion of testosterone into estradiol and the conversion of androstenedione into estrone, but it didn’t. The reason is quite simple. Chrysin is very poorly absorbed, so if you can’t get it into the body, you can’t expect it to work. Now I3C is a unique compound. It increases the ability of the liver to metabolize estrogen so that the body can urinate estrogen away more readily. Research on women shows that the minimum amount for the breast cancer reducing benefits of I3C is about 300 mg per day [18]. The guys getting Andro-6 received a dose of I3C (300 mg) that should have lowered their estrogen levels, yet their estrogen levels still increased. Additional research shows an increased excretion of estrogens after about 350-500 mg of I3C [19-24]. Perhaps more than 300 mg of I3C is needed to lower estrogen levels . However, what these studies don’t show is what happens to testosterone levels (and other hormones, for that matter). In fact, recent data from mice shows that I3C may lower testosterone levels and is considered an anti-androgen [25]. Based on all the available data, I3C doesn’t appear to be a valuable aid to the hard training bodybuilder or athlete.
Some people have figured that since I3C is converted into diindolylmethane (DIM), perhaps taking DIM would be better. DIM does act as an estrogen antagonist, which is a good thing for reducing risk of breast cancer [26, 27]. However, we don’t have any data on how it effects testosterone levels in men or if it could work for building muscle. Since it is a metabolite of I3C and I3C can lower testosterone levels, it may be wise to hold off on this agent until more is known about it.
What to Look For
There aren’t any published studies comparing the effectiveness of the current over-the-counter (OTC) prohormones, so while we may guess that 4-androstenediol is more anabolic than 4-androstenedione based upon preliminary research, it is still only a guess. There is some data on the drug versions of prohormones, that is the kind produced by drug companies, not supplement companies. Most assume that the two are the same, but they may not be. Based upon data using drug company manufactured prohormones, 4-androstenediol, 19-nor-4-androstenedione, and 19-nor-4-androstenediol appear to be the most anabolic. Most users will attempt to stack these agents in order to simulate a testosterone and Deca stack. Don’t kid yourself, prohormones are not able to equal the results of steroids, yet.
The traditional prohormone pills and capsules are very poorly absorbed. To circumvent this, supplement companies came out with cyclodextrin, micronized, and liposomal versions of prohormones. Cyclodextrins tend to spike concentrations in the blood so they need to be taken multiple times throughout the day to sustain blood levels. Micronized just makes the particles smaller, and smaller doesn’t always mean better absorption. Liposomes allow the prohormones to be absorbed through the lymphatic circulation, allowing for a sustained increase in blood levels. Which method is the best? Most of the experts in the field are claiming liposomal technology represents the cutting edge, right now. However, no comparative studies have been done yet. Research comparing each method of delivery using an equated amount of prohormone would certainly clear up some of the confusion.
If You Get Gyno
The first thing to do if you get gyno is to stop taking the prohormone product that caused the gyno. This may seem like common sense, but I get asked this all the time. “Hey man this stuff gave me gyno, should I keep taking it?” I’d like to reply, “Yes, keep taking it until your left breast catches up to your right breast,” but I don’t. Next set an appointment with your physician and have him check you over. You should be prepared to say exactly what you were taking, how much you were taking, and how long you were taking it. Hopefully you keep track of everything you do (like writing in a journal) so that you’ll be able to provide this information. Your doctor will guide you from there. You can still work out. If this happens while you have tried different prohormones, then you will need to seriously consider taking an aromatase inhibitor. Forget chrysin, it doesn’t work. Your doctor can guide you to some prescription agents that will work.
References
1. Liberti, L.E. and A. Der Marderosian, Evaluation of commercial ginseng products. J Pharm Sci, 1978. 67(10): p. 1487-1489.
2. Betz, J.M., et al., Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Ma Huang. J AOAC Int, 1997. 80(2): p. 303-315.
3. Gurley, B.J., P. Wang, and S.F. Gardner, Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography. J Pharm Sci, 1998. 87(12): p. 1547-1553.
4. Betz, J.M., K.D. White, and A.H. der Marderosian, Gas chromatographic determination of yohimbine in commercial yohimbe products. J AOAC Int, 1995. 78(5): p. 1189-1194.
5. Volpi, R., et al., Case report: finasteride-induced gynecomastia in a 62-year-old man. Am J Med Sci, 1995. 309(6): p. 322-325.
6. Miyamoto, H., et al., Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proc Natl Acad Sci U S A, 1998. 95(19): p. 11083-11088.
7. Seymour-Munn, K. and J. Adams, Estrogenic effects of 5-androstene-3 beta, 17 beta-diol at physiological concentrations and its possible implication in the etiology of breast cancer. Endocrinology, 1983. 112(2): p. 486-491.
8. Hackenberg, R., et al., Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androst-5-ene-3 beta,17 beta-diol in human mammary cancer cells. J Steroid Biochem Mol Biol, 1993. 46(5): p. 597-603.
9. Dorgan, J.F., et al., Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3 beta, 17 beta-diol to risk of breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev, 1997. 6(3): p. 177-181.
10. Dorgan, J.F., et al., Serum sex hormone levels are related to breast cancer risk in postmenopausal women. Environ Health Perspect, 1997. 105 Suppl 3: p. 583-585.
11. Nephew, K.P., et al., Studies of dehydroepiandrosterone (DHEA) with the human estrogen receptor in yeast. Mol Cell Endocrinol, 1998. 143(1-2): p. 133-142.
12. Rubino, S., et al., Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women. Maturitas, 1998. 28(3): p. 251-257.
13. Arlt, W., et al., Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab, 1999. 84(6): p. 2170-2176.
14. Gordon, C.M., et al., Changes in bone turnover markers and menstrual function after short- term oral DHEA in young women with anorexia nervosa. J Bone Miner Res, 1999. 14(1): p. 136-145.
15. Morales, A.J., et al., The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf), 1998. 49(4): p. 421-432.
16. Rodway, M.R., et al., Steroid regulation of progesterone synthesis in a stable porcine granulosa cell line: a role for progestins. J Steroid Biochem Mol Biol, 1999. 68(5-6): p. 173-180.
17. King, D.S., et al., Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial [see comments]. Jama, 1999. 281(21): p. 2020-2028.
18. Wong, G.Y., et al., Dose-ranging study of indole-3-carbinol for breast cancer prevention. J Cell Biochem Suppl, 1997. 29: p. 111-116.
19. Michnovicz, J.J., Increased estrogen 2-hydroxylation in obese women using oral indole-3- carbinol. Int J Obes Relat Metab Disord, 1998. 22(3): p. 227-229.
20. Michnovicz, J.J., H. Adlercreutz, and H.L. Bradlow, Changes in levels of urinary estrogen metabolites after oral indole-3- carbinol treatment in humans. J Natl Cancer Inst, 1997. 89(10): p. 718-723.
21. Bradlow, H.L., et al., Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev, 1994. 3(7): p. 591-595.
22. Michnovicz, J.J. and H.L. Bradlow, Dietary and pharmacological control of estradiol metabolism in humans. Ann N Y Acad Sci, 1990. 595: p. 291-299.
23. Michnovicz, J.J. and H.L. Bradlow, Induction of estradiol metabolism by dietary indole-3-carbinol in humans [see comments]. J Natl Cancer Inst, 1990. 82(11): p. 947-949.
24. Michnovicz, J.J. and H.L. Bradlow, Altered estrogen metabolism and excretion in humans following consumption of indole-3-carbinol. Nutr Cancer, 1991. 16(1): p. 59-66.
25. Wilson, V.S., et al., Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice. Environ Health Perspect, 1999. 107(5): p. 377-384.
26. Chang, Y.C., et al., Cytostatic and antiestrogenic effects of 2-(indol-3-ylmethyl)-3,3’- diindolylmethane, a major in vivo product of dietary indole-3-carbinol. Biochem Pharmacol, 1999. 58(5): p. 825-834.
27. Chen, I., et al., Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Carcinogenesis, 1998. 19(9): p. 1631-1639.
|
Resource Library HTML 
